DESCRIPTION (Applicant's Description): Candidate: The applicant is currently an Assistant Professor of Surgery at the University of Michigan. Prior to starting this first faculty position in 8-95, he was a resident in surgery at Johns Hopkins and then a fellow in surgical oncology at M.D. Anderson Cancer Center. He has a steadfast commitment to a career in academic surgery, and he strives to excel in patient care, laboratory research and teaching. To this end, he would like to continue his research training in a structured, mentored environment with the goal of becoming a competent and independent investigator. Environment: The research outlined in this proposal will be sponsored by Eric Fearon, M.D., Ph.D., an Associate Professor of Internal Medicine at the University of Michigan. Dr. Fearon is an internationally recognized expert in cancer genetics and tumor biology. Dr. Yahanda has dedicated bench space within his active and productive laboratory, as well as full access to the equipment and resources therein. Dr. Fearon and he have an outstanding w o r king relationship that will be an asset in fostering productive interactions and exchanges of ideas. The University of Michigan is a tremendous intellectual environment in which to work, collaborate, and study. There are nationally or internationally renowned experts on the faculty in virtually all disciplines who could serve as resources. Numerous core facilities are available within the Medical School and Cancer Center. A new NCI-designated Comprehensive Cancer Center recently opened which will further enhance the interactions between clinicians, basic scientists and physician researchers. Research: Mutations of the adenomatous polyposis coli (APC) gene are responsible for familial adenomatous polyposis (FAP). Individuals with FAP typically develop thousands of colorectal polyps, all of which have the potential to progress to cancer. There are subsets of individuals with APC mutations that do not have the typical phenotype, and instead, have few or absent colonic polyps and numerous extracolonic tumors. The APC protein binds to several other proteins including beta-catenin, glycogen synthase kinase-3beta (GSK-3beta), the human homolog of the Drosophila disks large protein (DLG), and a protein of unknown function, EB1. The applicants propose to evaluate whether the APC tumor suppressor pathway differs in cells of colonic and noncolonic origin. Specifically, they will examine the stability of the APC protein, expression and mutations of APC-associated proteins, and possible novel factors associated with APC in colonic and noncolonic tissues.